In patients with metastatic bone disease from prostate cancer, elevated markers of bone resorption and formation are significantly associated with increased risk of severe skeletal problems, disease progression, and death. Unfortunately, biomarkers of bone metabolism are not sensitive or selective enough for routine clinical use, providing only coarse risk stratification. We propose to apply the prognostic value of bone turnover to individual patients, by validating a novel method for high precision assessment of bone turnover in 50 prostate cancer patients with bony metastasis. Our proposal involves permanently labeling these individuals with a single small oral dose of the rare (but easily produced) 41Ca isotope, with negligible lifetime radioactive 41 exposure. Regular measurement of 41Ca abundance in small urine specimens over an 18 month observation period will enable an accurate assessment of bone turnover as well as a convenient long-term monitor of changes thereof, and at unprecedented sensitivity. In order to assess the ultimate utility of this novel method, 41Ca-based bone turnover measurements will be correlated with disease outcome and standard medical diagnostic techniques for advanced prostate cancer. We hypothesize that a urinary 41Ca assay utilizing accelerator mass spectrometry will be useful for risk assessment, disease staging, measurement of therapeutic efficacy, and sensitive detection of progressive bony disease. Our general goal for the proposed work is to translate a novel, safe, non-invasive, accurate, high precision method for bone turnover assessment into a clinical tool, providing oncologists with a new quantitative measure of cancer-induced changes in skeletal metabolism. Direct benefits of this project will be in minimizing the devastating consequences of late stage prostate cancer through more effective patient care, thereby improving patient quality of life and survival expectations. Ultimately, a validated 41Ca assay could also be useful in the detection and study of early metastatic spread, enabling systematic testing of therapies aimed at preventing this catastrophic disease state. [unreadable] [unreadable] [unreadable]